title: Estrogen promotes hepatic regeneration via activating serotonin signal.
abstract: The aim of this study was to determine if estrogen plays any role in the process of hepatic regeneration of nonligated lobe after portal vein branch ligation (PBL). We also investigated whether estrogen has any association with serotonin action during liver regeneration. Ovariectomized female rats with (E group) or without (non-E group) estrogen pellet were subjected to PBL on the left and middle lobes. Thereafter, the rats were killed, and blood, liver, and small intestine were sampled and analyzed. Sham animals underwent only ovariectomy and laparotomy. The E group showed a significantly greater regeneration rate than the non-E group at days 1, 2, and 7 after PBL. The activation of hepatic regeneration-related genes (such as IL-6, TNF-alpha, hepatic growth factor, c-fos, and c-myc) was also significantly higher in the E group as compared with the non-E group. Gene expression of serotonin receptor (5-HT2A) in the liver and tryptophan hydroxylase 1 in the small intestine were also up-regulated in the E group, indicating an activation of serotonin system in the E group. Additionally, total intestinal flow, portal venous flow, and hepatic arterial flow determined by fluorescent microsphere were significantly higher in the E group compared with the non-E group. Moreover, serotonin receptor antagonist (ketanserin) significantly attenuated liver regeneration rate in the E group. These results indicated that estrogen plays an important role in the process of liver regeneration after PBL. Our results also indicated that estrogen is at least partly related to the activation of serotonin system, which is also important in the process of liver regeneration.
authors.affiliation: Department of Surgery, Division of Surgical Oncology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Tomomi
authors.initials: T
authors.lastname: Kitagawa
authors.forename: Yukihiro
authors.initials: Y
authors.lastname: Yokoyama
authors.forename: Toshio
authors.initials: T
authors.lastname: Kokuryo
authors.forename: Toru
authors.initials: T
authors.lastname: Kawai
authors.forename: Katsutaka
authors.initials: K
authors.lastname: Watanabe
authors.forename: Kiyotaka
authors.initials: K
authors.lastname: Kawai
authors.forename: Masato
authors.initials: M
authors.lastname: Nagino
mesh_terms: D000818:Animals; D004967:Estrogens / Q000494:pharmacology*; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D007650:Ketanserin / Q000494:pharmacology; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008115:Liver Regeneration / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D012039:Regional Blood Flow / Q000187:drug effects; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012701:Serotonin / Q000378:metabolism*; D012702:Serotonin Antagonists / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D004967:Estrogens; D012702:Serotonin Antagonists; D012701:Serotonin; D007650:Ketanserin